Inorganic pyrophosphatase

Inorganic pyrophosphatase (PPA1) is a 289-amino acid enzyme that catalyzes the hydrolysis of inorganic pyrophosphate (PPi) to phosphate, a thermodynamically favorable reaction that drives numerous biosynthetic pathways forward (UniProt: Q15181). The protein is ubiquitously expressed and plays a housekeeping role in cellular metabolism, facilitating nucleotide synthesis, protein synthesis, and other anabolic processes.

PPA1 is relevant to Alzheimer's Disease pathology. In post-mortem human AD brain tissue compared to age-matched controls, PPA1 shows a modest but consistent upregulation with a mean log2 fold-change of +0.534 across subcellular fractions, measured by TMT-labeled quantitative proteomics (Chaparral AD proteomics). The elevation was detected in a single fraction within a four-fraction subcellular fractionation scheme (P2, P3, S2, S3). The functional significance of increased PPA1 levels in AD neurodegeneration remains to be determined, though dysregulation of energy metabolism and nucleotide synthesis are hallmarks of AD pathology.